Structural mechanism of a Rag GTPase activation checkpoint by the lysosomal folliculin complex

doi:10.1126/science.aax0364

GSTDTAP

DOI	10.1126/science.aax0364
	Structural mechanism of a Rag GTPase activation checkpoint by the lysosomal folliculin complex
	Lawrence, Rosalie E.1,2; Fromm, Simon A.1; Fu, Yangxue 1; Yokom, Adam L.1; Kim, Do Jin 1; Thelen, Ashley M.1,2; Young, Lindsey N.1; Lim, Chun-Yan 1,2; Samelson, Avi J.2,3; Hurley, James H.1,4,5; Zoncu, Roberto 1,2,4
	2019-11-22
发表期刊	SCIENCE
ISSN	0036-8075
EISSN	1095-9203
出版年	2019
卷号	366 期号:6468 页码:971-+
文章类型	Article
语种	英语
国家	USA
英文摘要	The tumor suppressor folliculin (FLCN) enables nutrient-dependent activation of the mechanistic target of rapamycin complex 1 (mTORC1) protein kinase via its guanosine triphosphatase (GTPase) activating protein (GAP) activity toward the GTPase RagC. Concomitant with mTORC1 inactivation by starvation, FLCN relocalizes from the cytosol to lysosomes. To determine the lysosomal function of FLCN, we reconstituted the human lysosomal FLCN complex (LFC) containing FLCN, its partner FLCN-interacting protein 2 (FNIP2), and the RagA(GDP):RagC(GTP) GTPases as they exist in the starved state with their lysosomal anchor Ragulator complex and determined its cryo-electron microscopy structure to 3.6 angstroms. The RagC-GAP activity of FLCN was inhibited within the LFC, owing to displacement of a catalytically required arginine in FLCN from the RagC nucleotide. Disassembly of the LFC and release of the RagC-GAP activity of FLCN enabled mTORC1- dependent regulation of the master regulator of lysosomal biogenesis, transcription factor E3, implicating the LFC as a checkpoint in mTORC1 signaling.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000498849000036
WOS关键词	GUANINE-NUCLEOTIDE-EXCHANGE ; REAL-SPACE REFINEMENT ; AMINO-ACID LEVELS ; CRYSTAL-STRUCTURE ; TUMOR-SUPPRESSOR ; MTORC1 ACTIVATION ; SCAFFOLD COMPLEX ; CRYO-EM ; RAGULATOR ; PROTEIN
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计	被引频次：112[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/226280
专题	环境与发展全球科技态势
作者单位	1.Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA; 2.Univ Calif Berkeley, Paul F Glenn Ctr Aging Res, Berkeley, CA 94720 USA; 3.Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94158 USA; 4.Univ Calif Berkeley, Calif Inst Quantitat Biosci, Berkeley, CA 94720 USA; 5.Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA
推荐引用方式 GB/T 7714	Lawrence, Rosalie E.,Fromm, Simon A.,Fu, Yangxue,et al. Structural mechanism of a Rag GTPase activation checkpoint by the lysosomal folliculin complex[J]. SCIENCE,2019,366(6468):971-+.
APA	Lawrence, Rosalie E..,Fromm, Simon A..,Fu, Yangxue.,Yokom, Adam L..,Kim, Do Jin.,...&Zoncu, Roberto.(2019).Structural mechanism of a Rag GTPase activation checkpoint by the lysosomal folliculin complex.SCIENCE,366(6468),971-+.
MLA	Lawrence, Rosalie E.,et al."Structural mechanism of a Rag GTPase activation checkpoint by the lysosomal folliculin complex".SCIENCE 366.6468(2019):971-+.